(1) To characterize and purify anti-desmosine antibodies and to develop sensitive immunological assays for monitoring urinary desmosine excretion in papain-treated hamsters and human emphysema subjects. (2) (a) To repeat experiments on enhancement of elastase secretion in cultured mouse periotoneal macrophages exposed to aqueous cigarette smoke solution, using alveolar macrophages (mouse). (b) To further characterize the purified mouse peritoneal macrophage elastase (determine MW, antigenic properties and reactions with endogenous proteinase inhibitors). (3) To examine (a) elastase: alpha 1 AT complexes in sera and lavage fluids of smokers for evidence of incomplete inactivation of the protease; and (b) levels of anti-oxidants (GSH-peroxidase, SOD) in cells and fluids of cigarette smokers with emphysema. (4) To test the effect of alpha 1 AT peptide fragments on alpha 1 AT synthesis in an intact animal model (rat) and in cultured human liver cells (SK-Hep-1), using homologous alpha 1 AT and immunochemical techniques. (5) To screen normal dog lungs for evidence of extracellular leukocyte elastase deposits, using antibody to dog leukocyte elastase and immunoperoxidase staining methods. The results will be correlated with parallel studies on human lung which were completed in the -07 grant period. (6) To repeat and confirm the demonstration of alpha 2 MG synthesis by cultured human alveolar macrophages.